title: New bichalcone analogs as NF-κB inhibitors and as cytotoxic agents inducing Fas/CD95-dependent apoptosis.
abstract: A series of novel bichalcone analogs were synthesized and evaluated in lipopolysaccharide (LPS)-activated microglial cells as inhibitors of nitric oxide (NO) and for in vitro anticancer activity using a limited panel of four human cancer cell lines. All analogs inhibited NO production. Compounds 4 and 11 exhibited optimal activity with IC(50) values of 0.3 and 0.5 μM, respectively, and were at least 38-fold better than the positive control. A mechanism of action study showed that both compounds significantly blocked the nuclear translocation of NF-κB p65 and up-regulation of iNOS at 1.0 μM. Compound 4 and three other analogs (3, 20, and 23) exerted significant in vitro anticancer activity GI(50) values ranging from 0.70 to 13.10 μM. A mode of action study using HT-29 colon cancer cells showed that 23 acts by inducing apoptosis signaling.
authors.affiliation: Department of Chemistry, National Cheng Kung University, Tainan 701, Taiwan.
authors.forename: M Vijaya Bhaskar
authors.initials: MV
authors.lastname: Reddy
authors.forename: Yuh-Chiang
authors.initials: YC
authors.lastname: Shen
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Bastow
authors.forename: Keduo
authors.initials: K
authors.lastname: Qian
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: C559076:1-(3-((4-(4-acetylphenyl)piperazin-1-yl)methyl)-4-hydroxy-5-methoxyphenyl)-3-(pyridin-3-yl)prop-2-en-1-one; C559075:1-(4-hydroxy-3-((4-(4-(3-(pyridin-3-yl)acryloyl)phenyl)piperazin-1-yl)methyl)phenyl)-3-(pyridin-3-yl)prop-2-en-1-one; D000970:Antineoplastic Agents; D047188:Chalcones; D011725:Pyridines; D051996:Transcription Factor RelA; D019014:fas Receptor; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II